{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:16:14Z","timestamp":1790727374737,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["169354"],"award-info":[{"award-number":["169354"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and\/or volume overload. Because the pathophysiological role of Scd1\/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL\/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 \u00b1 2.9% compared to 54.3 \u00b1 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.<\/jats:p>","DOI":"10.3390\/ijms22189883","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T21:37:12Z","timestamp":1631569032000},"page":"9883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation"],"prefix":"10.3390","volume":"22","author":[{"given":"Joshua","family":"Abd Alla","sequence":"first","affiliation":[{"name":"Molecular Pharmacology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya F.","family":"Jamous","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Quitterer","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland"},{"name":"Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","article-title":"Global public health burden of heart failure","volume":"3","author":"Savarese","year":"2017","journal-title":"Card. Fail. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1001\/jama.2020.10262","article-title":"Heart failure with reduced ejection fraction: A review","volume":"324","author":"Murphy","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","article-title":"Heart failure with preserved ejection fraction in perspective","volume":"124","author":"Pfeffer","year":"2019","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Writing Committee, Maddox, T.M., Januzzi, J.L., Allen, L.A., Breathett, K., Butler, J., Davis, L.L., Fonarow, G.C., Ibrahim, N.E., and Lindenfeld, J. (2021). 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: Answers to 10 pivotal issues about heart failure with reduced ejection fraction: A report of the American College of Cardiology Solution Set Oversight Committee. J. Am. Coll. Cardiol., 77, 772\u2013810.","DOI":"10.1016\/j.jacc.2020.11.022"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Askoxylakis, V., Thieke, C., Pleger, S.T., Most, P., Tanner, J., Lindel, K., Katus, H.A., Debus, J., and Bischof, M. (2010). Long-term survival of cancer patients compared to heart failure and stroke: A systematic review. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-105"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1074\/jbc.M115.702688","article-title":"Inhibition of G-protein-coupled receptor kinase 2 prevents the dysfunctional cardiac substrate metabolism in fatty acid synthase transgenic mice","volume":"291","author":"Graemer","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"190","DOI":"10.2174\/187152511797037583","article-title":"Up-regulation of the cardiac lipid metabolism at the onset of heart failure","volume":"9","author":"Abdalla","year":"2011","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.yjmcc.2005.08.002","article-title":"Transcriptome profiling of the canine tachycardia-induced heart failure model: Global comparison to human and murine heart failure","volume":"40","author":"Gao","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41540-018-0046-3","article-title":"A personalized, multiomics approach identifies genes involved in cardiac hypertrophy and heart failure","volume":"4","author":"Santolini","year":"2018","journal-title":"NPJ Syst. Biol. Appl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1055\/s-2008-1042429","article-title":"Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis","volume":"116","author":"Song","year":"2008","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E28","DOI":"10.1152\/ajpendo.90897.2008","article-title":"Biochemical and physiological functions of stearoyl-CoA desaturase","volume":"297","author":"Paton","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Matsui, H., Yokoyama, T., Sekiguchi, K., Iijima, D., Sunaga, H., Maniwa, M., Ueno, M., Iso, T., Arai, M., and Kurabayashi, M. (2012). Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033283"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3389\/fendo.2019.00726","article-title":"Induction of stearoyl-CoA 9-desaturase 1 protects human mesenchymal stromal cells against palmitic acid-induced lipotoxicity and inflammation","volume":"10","author":"Vertongen","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Iwai, T., Kume, S., Chin-Kanasaki, M., Kuwagata, S., Araki, H., Takeda, N., Sugaya, T., Uzu, T., Maegawa, H., and Araki, S.I. (2016). Stearoyl-CoA desaturase-1 protects cells against lipotoxicity-mediated apoptosis in proximal tubular cells. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111868"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1194\/jlr.M003780","article-title":"Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice","volume":"51","author":"Dobrzyn","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2014.11.003","article-title":"Metabolic reprogramming of the heart through stearoyl-CoA desaturase","volume":"57","author":"Dobrzyn","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1161\/CIRCHEARTFAILURE.112.967802","article-title":"Plasma phospholipid concentration of cis-palmitoleic acid and risk of heart failure","volume":"5","author":"Djousse","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/oxfordjournals.aje.a010038","article-title":"Plasma fatty acid composition and 6-year incidence of hypertension in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"150","author":"Zheng","year":"1999","journal-title":"Am. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1017\/S0007114507871674","article-title":"Serum fatty acid composition and indices of stearoyl-CoA desaturase activity are associated with systemic inflammation: Longitudinal analyses in middle-aged men","volume":"99","author":"Petersson","year":"2008","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/ajcn\/78.1.91","article-title":"Plasma fatty acid composition and incidence of diabetes in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"78","author":"Wang","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.yjmcc.2014.04.017","article-title":"Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction","volume":"74","author":"Suresh","year":"2014","journal-title":"J. Mol. Cell. Cadiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, L., and Yu, F. (2021). SCD leads to the development and progression of acute myocardial infarction through the AMPK signaling pathway. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-02011-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E357","DOI":"10.1152\/ajpendo.00471.2007","article-title":"Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart","volume":"294","author":"Dobrzyn","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.bbalip.2016.10.005","article-title":"Stearoyl-CoA desaturase 1 deficiency reduces lipid accumulation in the heart by activating lipolysis independently of peroxisome proliferator-activated receptor alpha","volume":"1861","author":"Bednarski","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yjmcc.2019.05.019","article-title":"Sirt1 counteracts decrease in membrane phospholipid unsaturation and diastolic dysfunction during saturated fatty acid overload","volume":"133","author":"Yamamoto","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e140785","DOI":"10.1172\/jci.insight.140785","article-title":"Neonatal hyperoxia inhibits proliferation and survival of atrial cardiomyocytes by suppressing fatty acid synthesis","volume":"6","author":"Cohen","year":"2021","journal-title":"JCI Insight"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1136\/hrt.2005.083345","article-title":"Circulating adiponectin concentrations in patients with congestive heart failure","volume":"92","author":"George","year":"2006","journal-title":"Heart"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.jacc.2008.07.073","article-title":"Resistin, adiponectin, and risk of heart failure the Framingham offspring study","volume":"53","author":"Frankel","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S1053-2498(98)00039-4","article-title":"Increased p53 protein expression in human failing myocardium","volume":"18","author":"Song","year":"1999","journal-title":"J. Heart Lung Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1161\/01.CIR.0000140973.60992.9A","article-title":"Increased collagen type I synthesis in patients with heart failure of hypertensive origin: Relation to myocardial fibrosis","volume":"110","author":"Querejeta","year":"2004","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1161\/01.RES.70.5.1006","article-title":"Isolation, characterization, and localization of cardiac collagen type VI. Associations with other extracellular matrix components","volume":"70","author":"Bashey","year":"1992","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/S0022-2275(20)37421-6","article-title":"Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes","volume":"38","author":"Vork","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yamamoto, T., Endo, J., Kataoka, M., Matsuhashi, T., Katsumata, Y., Shirakawa, K., Yoshida, N., Isobe, S., Moriyama, H., and Goto, S. (2018). Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208396"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.15252\/embr.201643426","article-title":"The ins and outs of endoplasmic reticulum-controlled lipid biosynthesis","volume":"18","author":"Jacquemyn","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1152\/physiolgenomics.00057.2004","article-title":"Cardiac transcriptional response to acute and chronic angiotensin II treatments","volume":"18","author":"Larkin","year":"2004","journal-title":"Physiol. Genom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1097\/00005344-200312001-00015","article-title":"Direct evidence for increased hydroxyl radicals in angiotensin II-induced cardiac hypertrophy through angiotensin II type 1a receptor","volume":"42","author":"Kakishita","year":"2003","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.biochi.2016.10.010","article-title":"Paraoxonase and atherosclerosis-related cardiovascular diseases","volume":"132","author":"Chistiakov","year":"2017","journal-title":"Biochimie"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s11427-016-0131-4","article-title":"Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice","volume":"59","author":"Pei","year":"2016","journal-title":"Sci. China Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1527-5299.2002.00717.x","article-title":"Reactive oxygen species, mitochondria, and NAD(P)H oxidases in the development and progression of heart failure","volume":"8","author":"Sorescu","year":"2002","journal-title":"Congest. Heart Fail."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1172\/JCI316","article-title":"Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell","volume":"101","author":"Leri","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10C","DOI":"10.1016\/S0002-9149(01)01507-7","article-title":"Angiotensin II and the pathophysiology of cardiovascular remodeling","volume":"87","author":"Williams","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.jhep.2008.03.018","article-title":"Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats","volume":"49","author":"Wei","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1210\/endo.138.4.5038","article-title":"Angiotensin increases lipogenesis in 3T3-L1 and human adipose cells","volume":"138","author":"Jones","year":"1997","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/sj.ijo.0803388","article-title":"Angiotensin II: A hormone that affects lipid metabolism in adipose tissue","volume":"31","author":"Goossens","year":"2007","journal-title":"Int. J. Obes."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rodriguez-Cuenca, S., Whyte, L., Hagen, R., Vidal-Puig, A., and Fuller, M. (2016). Stearoyl-CoA desaturase 1 is a key determinant of membrane lipid composition in 3T3-L1 adipocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162047"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.bbamem.2011.12.029","article-title":"Progress in understanding the role of lipids in membrane protein folding","volume":"1818","author":"Mitchell","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10925","DOI":"10.1016\/S0021-9258(19)50107-7","article-title":"Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver","volume":"267","author":"Ntambi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"183","DOI":"10.18388\/pb.2018_130","article-title":"The role of stearoyl-CoA desaturase in the regulation of cardiac metabolism","volume":"64","author":"Tabaczar","year":"2018","journal-title":"Postepy Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.jacl.2018.08.004","article-title":"Circulating oleic acid levels are related to greater risks of cardiovascular events and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis","volume":"12","author":"Steffen","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00535-009-0042-x","article-title":"Down-regulation of hepatic stearoyl-CoA desaturase 1 expression by angiotensin II receptor blocker in the obese fa\/fa Zucker rat: Possible role in amelioration of insulin resistance and hepatic steatosis","volume":"44","author":"Yokozawa","year":"2009","journal-title":"J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1007\/s00125-006-0444-8","article-title":"The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system","volume":"49","author":"Reuter","year":"2006","journal-title":"Diabetologia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23496","DOI":"10.1074\/jbc.M110.117481","article-title":"Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis","volume":"285","author":"Langer","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1097\/MOL.0b013e32833854ac","article-title":"Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: Considerations for future drug discovery","volume":"21","author":"Brown","year":"2010","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/ATVBAHA.109.198036","article-title":"Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis","volume":"30","author":"Brown","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1248\/bpb.b12-00702","article-title":"A novel inhibitor of stearoyl-CoA desaturase-1 attenuates hepatic lipid accumulation, liver injury and inflammation in model of nonalcoholic steatohepatitis","volume":"36","author":"Kurikawa","year":"2013","journal-title":"Biol. Pharm. Bull."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1021\/jm200319u","article-title":"Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia","volume":"54","author":"Oballa","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1093\/jn\/131.9.2260","article-title":"Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid","volume":"131","author":"Miyazaki","year":"2001","journal-title":"J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9180","DOI":"10.1016\/S0021-9258(18)31568-0","article-title":"Isolation and characterization of the mouse cardiac myosin heavy chain genes","volume":"266","author":"Gulick","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Quitterer, U., Fu, X., Pohl, A., Bayoumy, K.M., Langer, A., and AbdAlla, S. (2019). Beta-arrestin1 prevents preeclampsia by downregulation of mechanosensitive AT1-B2 receptor heteromers. Cell, 176.","DOI":"10.2139\/ssrn.3188449"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fmed.2018.00359","article-title":"Sensitization of the angiotensin II AT1 receptor contributes to RKIP-induced symptoms of heart failure","volume":"5","author":"Wolf","year":"2019","journal-title":"Front. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.bbrc.2011.05.041","article-title":"A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor","volume":"409","author":"Quitterer","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9883\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:02:02Z","timestamp":1760166122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,13]]},"references-count":62,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189883"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189883","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,13]]}}}